The protein p300, named for its 300 kd molecular weight, was first identified by Yee et al., 1985, Virology 147:142-153. p300, p107, and p130 are three of possibly numerous other human cellular proteins that associate with adenovirus E1A protein in immunoprecipitation experiments (Harlow et al., 1986, Molecular and Cellular Biol. 6:1597). The association of p300 with E1A appears to be necessary although insufficient for establishment of the transformed state by adenovirus (i.e., the ability of adenovirus to stimulate a normal, quiescent cell into a malignant one). Since its identification, the interaction of p300 with E1A has been widely studied; its molecular cloning, however, has been elusive due to its exceedingly large size.
Because of its involvement in adenovirus transformation, p300 is considered, like the RBp protein associated with the retinoblastoma susceptibility gene (which also binds the E1A protein), to be a negative regulator of cell growth that is at least partially inactivated by the E1A protein.
Besides stimulating the S-phase entry of quiescent cells, the region of E1A interacting with p300 is also responsible for repressing a number of transcriptional enhancers and promoters. The first identified targets for E1A repression were the viral enhancers of the SV40 and polyoma virus and the enhancer controlling the transcription of the E1A gene itself. In addition to this group of viral enhancers, a second class of enhancers and promoters driving transcription of tissue specific cellular genes associated with the terminal differentiation state of a cell were found to be repressed by E1A.
p300 and p300-associated proteins have been reported to be components of TATA-binding protein complexes (Abraham et al., 1993, Oncogene 8:1639). It has been observed that E1A mutants defective for p300 binding are also defective for an E1A-induced function that represses enhancer-mediated tissue-specific gene expression. This observation underlines the suggestion in the art that p300 may play a role in enhancer-stimulated expression of tissue-specific genes. A p300 consensus DNA-binding sequence has been proposed which shows some similarity to certain E1A-targeted enhancer elements (Abraham et al., 1993, supra).